The Signal in the Noise: Size and Dynamics of Topological Domains Based on DNA Fluctuations

Within the cell, long DNA molecules carry genetic information and must be stored in a way that keeps them accessible so they can interact with various biomolecules that control the reading and processing of this information. DNA-binding proteins often play a role in these processes by bringing two distant sites on the DNA closer together, thereby inducing transient topological domains. 

The work presented in this seminar demonstrates how taking into account fluctuations in DNA length, in addition to the average length, provides additional insights into protein-DNA interactions that would otherwise remain undetectable.

The NUMEV Seminars are open to a wide audience of students and researchers from all disciplines who wish to learn more about the current research areas of the NUMEV-MIPS community (Mathematics, Computer Science, Physics, and Systems) or about opportunities to develop their skills and expertise.

“The Signal in the Noise: Size and Dynamics of Topological Domains from DNA Fluctuations”

Enrico Carlon, Soft Matter and Biophysics, KU Leuven, Belgium

Abstract

Within the cell, long DNA molecules carry genetic information and must be stored while remaining accessible to interact with various biomolecules that regulate their reading and processing. DNA-binding proteins often mediate these processes by bringing two distant DNA sites together, thereby inducing (transient) topological domains. To understand the dynamics and molecular architecture of protein-induced topological domains in DNA, quantitative and time-resolved approaches are required.

Here we present a methodology for determining the size and dynamics of topological domains through the analysis of fluctuations: a protein-binding event causes a decrease in the variance of the end-to-end distance of a stretched, supercoiled DNA molecule. Using a combination of high-speed magnetic tweezers experiments, Monte Carlo simulations, and analytical theory, we map the dependence of DNA extension fluctuations on supercoiling density and external force. We demonstrate how transient (partial) dissociation of DNA-bridging proteins results in dynamic sampling of different topological states.

Our work demonstrates that taking into account fluctuations in DNA extension, in addition to the average extension, provides additional insights and allows for the investigation of protein-DNA interactions that would otherwise remain undetectable.